Expression and function of Set7/9 in pancreatic islets.

Takeshi Ogihara, Nathan L. Vanderford, Bernhard Maier, Roland W. Stein, Raghavendra G. Mirmira

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Histone tail acetylation and methylation are known to enhance accessibility of islet genes to transcription factors and the basal transcriptional machinery.  In this brief report, we follow up on a recent study in which we identified the islet enriched factor Set7/9 as a potentially important histone methyltransferase in β-cells (Deering, et al. Diabetes 2009; 58:185-93).  We had suggested that the methylation of H3-Lys4 by Set7/9 enhances accessibility of the insulin gene to the basal transcriptional machinery.  Consistent with this hypothesis, we show here that RNA polymerase II occupancy at the insulin and IAPP genes is considerably enhanced in β-cells compared to α cells (or NIH3T3 cells), and that the converse is true for RNA polymerase II occupancy at the glucagon gene. The enrichment of Set7/9 in β-cells appears to be dependent upon Pdx1, as knockdown of Pdx1 in INS-1 β-cells using small hairpin RNAs almost completely abolishes Set7/9 expression.  A LacZ expression vector driven by the -6.5 kilobase pair Set7/9 promoter that contains putative Pdx1 binding sites shows β-cell-line-specific expression.  Taken together, our data support further the hypothesis that Pdx1-dependent Set7/9 expression may be crucial to enhancing chromatin accessibility and transcription of β-cell genes.

Original languageEnglish
Pages (from-to)269-272
Number of pages4
JournalIslets
Volume1
Issue number3
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
This work was supported by grants from the National Institutes of Health (R01 DK60581 to R.G.M.; R01 DK50203 to R.W.S.; 5T32 DK007061 to N.L.V.) and by a Juvenile Diabetes Research Foundation Grant (to R.G.M.).

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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